Our objective is to develop and validate in-vivo somatic cell mutation assay methods, applicable to rabbits, Rhesus monkeys and humans, that measure the level of base substitution mutations produced to genetically toxic agents to be monitored in individual humans and compared with identical effects measured in experimentally exposed animals. Our approach entails measuring the fraction of circulating erythrocytes that contain any one of a specific set of amino acid-substituted variants of the proteins hemoglobin and spectrin. Such cells will be labeled with fluorescently conjugated antibodies specific for the variant proteins and enumerated using automated cytofluorometric methods. The critical element in our approach is a method for producing polyvalent antisera tht can recognize ten or more different, mutationally inducible, amino acid-substituted variants of either hemoglobin or spectrin. We exploit the sequence differences between homologouos proteins from different mammalian species; the protein from one speciews serves as an immunologic model for a collection of point mutations in the same protein of other species, e. g., rabbits immunized with human hemoglobin produce polyvalent antisera each component of which should monospecifically recognize one rabbit to human amino acid jsubstitution in rabbit hemoglobin. Rabbit sera against human hemoglobin and spectrin are being produced to verify that they will detect mutations in the corresponding rabbit proteins and to develop an animal model for later controlled exposure studies. Since monkey and human protein sequences are very similar, the method can be extended to humans using Rhesus monkeys as immunologic surrogates. Sera raised in Rhesus would be directly applicable for detecting essentialy the same point mutations in Rhesus as in humans.